Breast cancer is one of the leading causes of death for women. About one out of eight or nine women are expected to develop tumors of the breast, and about one out of sixteen to twenty are expected to die prematurely from breast cancer. Mammography or other X-ray methods are currently most used for detection of breast cancers. However, every time a mammogram is taken, the patient incurs a small risk of having a breast tumor induced by the ionizing radiation properties of the X-rays used during the mammogram. Also, the mammography X-ray process is costly and sometimes imprecise. Accordingly, the National Cancer Institute has not recommended mammograms for women under fifty years of age, who are not as likely to develop breast cancers as are older women. However, while only about twenty two percent of breast cancers occur in women under fifty, data suggests that breast cancer is more aggressive in pre-menopausal women. Furthermore, women under forty are getting the disease in increasing numbers--about eleven thousand annually now-and no one knows why.
Mammograms require interpretation by radiologists. One radiologist has said "I generally can spot cancers between five and ten millimeters in diameter. The prognosis is excellent then." However, about ten to fifteen percent of tumors of this size are not detected. One study showed major clinical disagreements for about one-third of the same mammograms that were interpreted by a group of radiologists. Further, many women find that undergoing a mammogram is a decidedly painful experience.
Thus, alternative methods to detect breast cancers are needed, especially non-invasive methods that do not entail added risks, that can detect tumors as small as two millimeters in diameter, that are not unduly unpleasant to the patient, and that can be used for early detection. Such a screening system is needed because extensive studies have demonstrated that early detection of small breast tumors leads to the most effective treatment. While X-ray mammography can detect lesions of approximately five mm or larger, the accuracy may range between 30% and 75%, depending on the skill of the diagnostic radiologist. Repeated X-ray examinations, however, are not encouraged because these may become carcinogenic. These considerations, in addition to cost considerations, have led physicians to recommend that women wait until the age of fifty before having routine mammograms.
One solution would be a non-ionizing, non-invasive, and low cost detection or screening method to detect very small malignant breast tumors. It could greatly increase without hazard the number of patients examined and would identify those patients who need diagnostic X-ray examinations, where the added hazards and costs could be justified.
About one in eight women develop breast cancers and about one in sixteen die prematurely from this disease. Despite strong encouragement, less than half of the millions of women who should be are routinely screened. Some of the reasons are cost and discomfort experienced during mammography. Other concerns are the additional risks associated with ionizing radiation, especially for routine exams for women under fifty. However, while only twenty two percent of breast cancers occur in women under fit, data suggest that breast cancer is more aggressive in pre-menopausal women. A screening procedure need only identify breasts with abnormalities. The precision and imaging requirements associated with diagnostic purposes and treatment monitoring, while desirable, need not apply.
Further, mammography fails to detect between five and twenty-five percent of malignant breast cancers. While many tumors are detected by mammography, the method is not capable of determining whether the tumor is benign or malignant. When a tumor is detected, a biopsy must be made to determine the nature of the tumor. Less than twenty percent of the tumors detected in mammograms are found to be malignant, but the biopsy is both painful and costly. Thus, a complementary method is needed that uses a different modality, such as microwaves, that may be beneficial in reducing the number of false negatives and false positives.
There are several generic cancer detection methods: sonic, chemical, nuclear and non-ionizing electromagnetic. The sonic, chemical and nuclear (such as MRI) techniques have been under study for some time and, while some interesting approaches are being followed, none have been publicized as being available in the near future for low cost screening.
The method described herein is not like the known non-ionizing electromagnetic methods. Studies have considered the use of electromagnetic, non-ionizing methods to detect or image portions of the human body. An excellent summary of such activity is presented in a publication entitled "Medical Applications of Microwave Imaging", edited by L. E. Larsen and J. H. Jacobi, IEEE Press 1986.* These activities include microwave thermography, radar techniques to image biological tissues, microwave holography and tomography, video pulse radar, frequency modulation pulse compression techniques for biological imaging, microwave imaging with diffraction tomography, inverse scattering approaches, and medical imaging using an electrical impedance. The publications in this book contain about five hundred citations, some of which are duplicates. The technology cited not only includes electromagnetic disciplines, but also notes related studies in sonic imaging and seismic imaging. To update these data, the IEEE transactions on Medical Imaging, Biomedical Engineering, Microwave Theory and Techniques and Antennas and Propagation have been reviewed. Also surveyed was the publication Microwave Power and Engineering. This update has indicated little significant progress in the aforementioned electromagnetic techniques that would be important to detect breast and prostate cancers. In these publications breast and prostate cancer detection systems based on the concepts described in this specification were not presented. FNT * See the list of references at the end of this specification.
Many important reasons exist for this lack of progress. In the case of microwave thermography, adequate depth of penetration, along with the required resolution, may not be realized, except for large cancers. In the case of holography, reflections at the skin-air interface tend to mask the desired returns from breast tumors beneath the skin. Further, illuminating the entire volume of a breast either requires excessive power (with possible biological hazards) or acceptance of poor signal-to-noise ratios. In the case of through-the-body electromagnetic techniques, such as tomography, the attenuation characteristics of the body are such that long wavelengths are usually used, with an attendant loss of resolution. Imaging by determining perturbations in body impedance caused by the presence of tumors as sensed by multi-electrode arrays have been either inadequate in sensitivity or subject to false alarms. A major difficulty with some of the multi-electrode or multi-antenna systems is that matrix methods are used to process the measured data into an image. With such methods, small errors in the measurements or assumptions are often enlarged during processing. Other problems, such an ambiguous or inconclusive results, may occur with the computational matrix method itself.
More recently, two microwave methods have been proposed to detect breast cancers. Both employ no more than a few narrow-band, fixed frequencies. One such method applies unfocused 900 megahertz energy directly to the breast via a resonant, open faced cavity applied directly to the breast. Some promising preliminary clinical results have been claimed if the data from adjacent breasts is compared. However, inconclusive results may occur in the vicinity of the nipple, where substantial variations in skin thicknesses occur. The other method proposes scanning a breast with a microwave beam via a dielectric slab pressed against the breast. The so-called beam of this method was relatively broad because it was developed by an open-ended wave guide pressed against the slab. The waveguide did not embody focusing features. As a result, reflections from many incidental scatterers not near a possible tumor could be expected. Such reflections could mask the desired returns. Further, it is nearly impossible to press such a plate uniformly against the breast without developing some air gaps that can cause massive reflections. Studies demonstrate that the use of such a plate is disadvantageous and results in excessive reflections and reverberations from the skin that may mask any desired return.
The present method is not like thermography, which uses the passive microwave or infrared emissions generated by malignant tumors which exhibit elevated temperatures with respect to normal breast tissue. Such radiated emissions must first pass through the normal breast tissue, then through the skin to a sensor placed on or external to the breast. Systems that have used such passive emissions have been clinically evaluated. A substantial number of analyses have been conducted, including a few that have considered but have not resolved the perturbing effects of the skin. The results are viewed as less efficacious than other detection modalities, such as X-ray mammography.
The present method is also unlike hyperthermia methods that are designed to heat malignant tumors in situ, preferentially over normal breast tissues. Typically, an antenna or an array of antennas are placed near or over the breast. Fixed frequency, microwave energy generally below three GHz is then directed into the breast through the skin, through normal breast tissue and thence to the tumor. In some cases, electronically controllable phased arrays have been considered. The heating of the tumor has been optimized by invasively emplacing a sensor in the tumor; the sensor provides feedback signals to the electronic controls of the phased array to adjust the phase of each antenna for best results.
In summary, many, if not all of the past microwave methods, such as those used in thermography, hyperthermia or microwave imaging or detection, have experienced difficulties because breast tissues are not homogeneous; they are heterogeneous. A principal heterogeneity is associated with the skin, especially near a breast nipple. In addition, the dielectric parameters of the breast of one human may be significantly different than the dielectric parameters of other humans. Another problem is the necessity to focus the microwave energy into as small a spot or voxel as possible so as to be able to resolve very small tumors. This is best done by resorting to the smaller wavelengths or higher frequencies, frequencies well above those typically used for most of the reported therapeutic or imaging electromagnetic systems. However, such use of higher frequencies increases the difficulty of coping with skin-introduced heterogeneity effects.
The methods and apparatus described herein envision an illuminator or antenna that propagates focused, short duration pulses of low power microwave beams into the breast or other tissues. The focusing may be effectively achieved either physically by lenses, reflectors, or phased arrays, or artificially by synthetic aperture methods. The pulses may be generated by pulse sources or synthetically by swept-frequency, Fourier inversion methods. When these effectively focused beams encounter a tumor, more energy is returned than from normal breast tissue. This occurs because a malignant tumor has significantly greater dielectric parameters than are exhibited by normal tissues. The backscatter returns from a possible tumor are captured by a collector that is also a part of the antenna and may be effectively focused in the region of the expected tumor. By carefully focusing the power into a small volume or voxel within the breast and scanning the focal point from the skin to chest wall and from side to side, tumors can be detected and imaged.
Unwanted returns from heterogeneity in the breast are suppressed by several methods. One method is the use of a wide-aperture, confocal illuminator and collector. Typically, many of the features of the illuminator and collector may share the same position or function. Such a wide-aperture, con-focal design tends to average out minor variations in the dielectric parameters as well and to suppress returns from sources not near the focal point. Another method is to illuminate the breast or other tissues with short duration pulses, whether generated synthetically or in real time, to isolate the returns from scatters adjacent to a possible tumor and to compensate for propagation losses.
Specifically, the preferred apparatus of the disclosed system employs short duration pulses (either in real time or synthetically generated) in combination with a multi-antenna array (realized either physically or synthetically). The perturbations introduced by the skin-related interfaces and any other heterogeneity in the breast or other tissue are detected and are used to suppress the unwanted effects of such perturbations. Such suppression may include a determination of the skin's thickness and its dielectric parameters. Another method uses electronically controllable phased or synthetic arrays. Such arrays, in combination with signal processing, can develop the approximate dielectric parameter of each breast or other tissue segment.
Such methods also can be used to determine whether or not a tumor is malignant or benign by noting the amplitude of the returns; malignant tumors usually exhibit much larger returns than benign tumors. All of the aforementioned techniques that are useful to suppress heterogeneity are also useful to help resolve whether tumors are benign or malignant.
This invention and improvements described in this application were first proposed to two government Federal agencies. Four proposals were rejected because the group of experts that reviewed them did not believe the concept would work. A fifth proposal was funded if only extensive computer simulations were conducted to demonstrate feasibility. Although the proposals incorporated technology that was proven in other areas, such as conventional radar, video-pulse radar or confocal microscopy, the review panels did not believe such technology would be viable when applied to the human breast. Some of the reasons given were that the human breast is opaque to microwaves, that the dielectric difference between normal and malignant tissues is too small for reliable detection, that resonant scattering enhancement could not occur for a tumor immersed in normal breast tissue, that the backscatter effects from heterogeneity would mask returns from malignant tumors, and that the microwave method lacked resolution needed to detect small tumors or microcalcifications. This issue of viability was put to rest only after extensive computer-aided studies that required some 250 hours of Cray computer time.